Abstract

Background

Protein kinase C (PKC) in the spinal cord appears to mediate chronic injury-induced
pain, but not acute nociceptive pain. Muscle insult results in increased release of
glutamate spinally, and hyperalgesia that is reversed by spinal blockade of NMDA and
non-NMDA glutamate receptors. Therefore, we hypothesized that spinal activation of
PKC 1) mediates the late phase of hyperalgesia 1 week after muscle insult, and 2)
produces mechanical hyperalgesia through activation of NMDA and non-NMDA glutamate
receptors.

Results

Rats were implanted with intrathecal catheters for delivery of drugs directly to the
spinal cord. Mechanical withdrawal thresholds of the paw were determined using von
Frey filaments. Intrathecal phorbol 12,13 dibutyrate (PDBu) produced a dose-dependent
decrease in the mechanical withdrawal threshold of the paw that was prevented by pretreatment
with the PKC inhibitor, GF109203X. Pretreatment with an NMDA receptor antagonist (AP5)
or a AMPA/kainate receptor antagonist (NBQX) prevented the decrease in mechanical
withdrawal threshold by PDBu. Two injections of acidic saline in the gastrocnemius
muscle decreased the mechanical withdrawal thresholds of the paw bilaterally 24 h
and 1 week after the second injection. However, blockade PKC in the spinal cord had
no effect on the decreased withdrawal thresholds of the paw when compared to vehicle
controls.

Conclusion

Spinal activation of PKC produces mechanical hyperalgesia of the paw that depends
on activation of NMDA and non-NMDA receptors. Chronic muscle-induced mechanical hyperalgesia,
on the other hand, does not utilize spinal PKC.